Glutamine metabolic inhibitor-containing liposome and pharmaceutical composition and use thereof

Abstract

The invention relates to a glutamine metabolic inhibitor-containing liposome and a pharmaceutical composition and use thereof. The fat-soluble glutaminase allosteric site inhibitor and the antitumor activity in combination with other drugs are obviously improved. The pharmacological activity of a glutamine metabolic inhibitor is further enhanced by increasing the solubility of the poorly water-soluble glutamine metabolic inhibitor by a lipophilic part of the liposome and modifying the liposome adjunct such as polymethacrylate; through the screening optimization of a formula, the inhibition rate of tumor cells is increased and finally the preparation is evaluated through an animal subcutaneous tumor model; the experimental results show that the liposome can significantly improve the anti-tumor activity of the glutamine metabolic inhibitor and improve the animal survival rate.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a novel dosage form liposome formula, which can significantly improve the antitumor activity of fat-soluble glutaminase allosteric site inhibitors and other drugs combined with them. Background technique [0002] Liposome, as a drug-loaded preparation, is an earlier and most mature preparation in clinical application. Liposome (liposome) is an artificial membrane. The hydrophilic head of phospholipid molecules is inserted into the water, and the hydrophobic tail of the liposome faces the air. After agitation, spherical liposomes with bilayer lipid molecules are formed, with diameters ranging from 25 to 1000 nm. . Utilizing the feature that liposomes can fuse with cell membranes, drugs can be delivered into cells. Drugs approved by the U.S. FDA include amphotericin B and doxorubicin liposome. [0003] Allosteric site inhibitors of glutaminase are inhibitors of tumor metabo...

AI Technical Summary

Problems solved by technology

However, the BPTES and CB-839 compounds reported in the literature, as well as our newly discovered glutaminase allosteric sites and / or inhibitors of glutamate dehydrogenase, all have the characteristics of poor solubility; in order to increase the solubility of these compounds properties, we investigated the effect of liposomes containing various additives on the pharmacological properties of the compounds

[0004] Polymethacrylate is widely used in pharmaceutical preparations, but reports of using it to modify liposomes are relatively rare; recently, it has been reported that polymethacrylate modification can significantly improve liposome stability, skin penetration , encapsulation efficiency, adhesion, etc.; we tried a variety of polymethacrylates to improve the antitumor pharmacological activity of the compound; at the same time, we investigated the synergistic interaction of the combined drug on the liposome of the glutamine metabolism inhibitor Effects and Mode of Administration of Liposomes

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